Treatment with ibrutinib may be associated with development of hypertension and risk for adverse cardiovascular events, according to study results published in Blood.
Although ibrutinib has shown significant efficacy as a therapeutic agent for patients with B-cell malignancies, there are growing concerns about its use and long-term cardiotoxicity. Researchers examined 562 consecutive patients treated with ibrutinib for B-cell malignancies between 2009 and 2016. Mean age was 63.8 years and 70.6% of patients were male. In this cohort, 73.8% of patients had chronic lymphocytic leukemia (CLL), and most patients received ibrutinib following relapse.
The researchers compared the incidence of new or worsened hypertension and with Framingham-predicted incident hypertension rates. They also assessed the development of other major adverse cardiovascular events, as well as the preventive and modulatory effects of antihypertensive medications.
After a median follow-up of 30 months, 78.3% of patients taking ibrutinib developed new or worsening hypertension, with 37.6% of patients developing grade 3 or 4 hypertension. Multivariable analysis showed that CLL (P =.004), CYP3A4 inhibitor (P =.02), and baseline systolic blood pressure (P <.001) were associated with hypertension development.
Major adverse cardiovascular events occurred in 16.5% of patients overall and were more common in patients with new or worsened hypertension compared with patients with no or stable hypertension (19.1% vs 8.2%; P =.03). Adverse cardiovascular events included arrhythmias, myocardial infarction, stroke, heart failure, and cardiovascular death. In multivariable regression analysis, new or worsening hypertension was found to be associated with increased major adverse cardiovascular events (hazard ratio, 2.17; P =.03).
No specific class of antihypertensive medication was associated with prevention or control of ibrutinib-related hypertension. However, initiation of antihypertensive therapy overall was associated with lower risk for major adverse cardiovascular events (hazard ratio, 0.40).
The researchers concluded that ibrutinib is associated with a significantly elevated risk for early-onset hypertension and additionally may be associated with long-term risk for developing major cardiac events, including incident arrhythmias. Further studies assessing the etiology and treatment of hypertension development during treatment with ibrutinib are warranted.
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
1. Dickerson T, Wiczer T, Waller A, et al. Hypertension and incident cardiovascular events following ibrutinib initiation [published online October 3, 2019]. Blood. doi:10.1182/blood.2019000840